Secondary Pulmonary Alveolar Proteinosis Research Articles

A patient with multiple myeloma and respiratory insufficiency due to accumulation of paraprotein in the alveolar space

We describe a patient with multiple myeloma and respiratory insufficiency. Autopsy revealed accumulation of IgG-kappa paraprotein in the alveolar space. The clinical and pathological presentation are typical for secondary pulmonary alveolar proteinosis. Attention is focussed on the possibility of secondary pulmonary alveolar proteinosis as a cause for dyspnoea in patients with haematological malignancies.

Secondary alveolar proteinosis is a reversible cause of respiratory failure in leukemic patients.

We report here our experience of secondary pulmonary alveolar proteinosis (PAP) in patients with hematologic malignancies. The diagnosis of PAP was made by bronchoalveolar lavage (BAL) and based on the identification of periodic acid-Schiff-positive proteinaceous material with the characteristic ultrastructural pattern. Ten patients with leukemia and secondary PAP are described. Three patients had received bone marrow transplants. Data obtained from sequential BAL have shown that at least four of them--all of them achieving complete remission or recovery from neutropenia after bone marrow transplantation--had reversible PAP, and we emphasize this potential reversibility. Furthermore, in order to estimate the frequency of PAP in hematologic patients, we retrospectively studied 113 episodes of pneumonia occurring in our department over a 2-yr period. The incidence of secondary PAP in patients with pulmonary symptoms was so estimated at 5.3% among all the hematologic population, and to 10% in patients with myeloid disorders. This report (1) confirms that BAL is an accurate way to diagnose PAP in immunocompromised hosts, (2) emphasizes that PAP is not an unusual cause of respiratory failure in this population and that it is strongly associated with myeloid disorders, and (3) shows that secondary PAP is potentially reversible, especially if complete remission of the underlying disease is achieved.

Pulmonary Alveolar Proteinosis Associated with Pneumocystis carinii: Ultrastructural Identification in Bronchoalveolar Lavage in AIDS and Immunocompromised Non-AIDS Patients

Pneumocystis carinii (PC) has been recognized as frequently responsible for most opportunistic pulmonary infections occurring in immunocompromised AIDS and non-AIDS patients. Moreover, these patients can be considered at risk for secondary pulmonary alveolar proteinosis. Therefore, we have investigated the occurrence of associated secondary alveolar proteinosis and PC pneumonitis in AIDS and non-AIDS immunocompromised patients. In a series of 26 bronchoalveolar lavages (BAL) in patients with PC pneumonitis (19 AIDS and seven non-AIDS patients), we observed on light microscopy, in addition to the honeycombed material, areas of an extracellular material that had a different pattern which was suggestive of that described in alveolar proteinosis. A systematic ultrastructural study of these 26 BAL fluid samples demonstrated in each of them an accumulation of phospholipid surfactantlike extracellular material mixed or not with the PC cysts. In nine cases, the observation of lipoproteinaceous material on light microscopy and abundant phospholipid material with myelinlike and myelin tubular laminated structures on electron microscopy was highly suggestive of an associated pulmonary alveolar proteinosis (PAP). Such an accumulation of extracellular material was not observed in the 11 BAL fluid samples collected in immunocompromised patients (seven AIDS and four non-AIDS patients) without PC pneumonitis. These findings demonstrated a particular frequency of associated PAP with PC pneumonitis. These results raise important questions concerning (1) the consequence of such an alveolar accumulation of lipoproteinaceous material on the clinical status and prognosis of the pneumonitis, and (2) the mechanisms responsible for this accumulation.

Secondary pulmonary alveolar proteinosis occurring in two patients with acquired immune deficiency syndrome

This report describes two patients with acquired immune deficiency syndrome (AIDS) in whom respiratory failure and opportunistic infection associated with secondary alveolar proteinosis developed. In one patient, the alveolar proteinosis was apparently secondary to Mycobacterium tuberculosis and in the other to Pneumocystis carinii and cytomegalovirus infection. Both patients died of respiratory failure, and it was suspected that secondary alveolar proteinosis could have been a contributing cause of death.

Pulmonary alveolar proteinosis.

The term pulmonary alveolar proteinosis (PAP) comprises a heterogeneous group of rare disorders characterized by abundant deposition of surfactant- and lipoproteins in the alveoli. The autoimmune form accounts for 90% of cases and is characterized by the presence of GM-CSF autoantibodies. Secondary PAP is associated with several underlying conditions, mainly hematologic malignancies, infections and inhalation exposure, and is GM-CSF antibody negative. Several conditions can mimic PAP, in particular the radiological findings: the crazy paving pattern on high resolution computed tomography (HRCT) is common also to infections, neoplasms, and other interstitial lung diseases. Bronchoalveolar lavage (BAL) typical findings and the detection of serum GM-CSF antibodies are usually sufficient for the diagnosis of PAP. Whole lung lavage (WLL) is still the gold standard for treatment of PAP and is followed by complete remission in about 50% of cases. Inhalative treatment with GM-CSF alone or in combination with WLL could represent the future approach for patients with autoimmune PAP refractory to WLL alone. The anti CD-20 antibody rituximab represents a further promising approach for autoimmune PAP. The treatment of secondary PAP should be focused on the underlying disease.